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The MEGA-PRESS method is the most common method used to measure γ-aminobutyric acid (GABA) in the brain at 3T. It has been shown that the underestimation of the GABA signal due to B0 drift up to 1.22 Hz/min can be reduced by post-frequency alignment. In this study, we show that the underestimation of GABA can still occur even with post frequency alignment when the B0 drift is up to 3.93 Hz/min. The underestimation can be reduced by applying a frequency shift threshold. A total of 23 subjects were scanned twice to assess the short-term reproducibility, and 14 of them were scanned again after 2–8 weeks to evaluate the long-term reproducibility. A linear regression analysis of the quantified GABA versus the frequency shift showed a negative correlation (P < 0.01). Underestimation of the GABA signal was found. When a frequency shift threshold of 0.125 ppm (15.5 Hz or 1.79 Hz/min) was applied, the linear regression showed no statistically significant difference (P > 0.05). Therefore, a frequency shift threshold at 0.125 ppm (15.5 Hz) can be used to reduce underestimation during GABA quantification. For data with a B0 drift up to 3.93 Hz/min, the coefficients of variance of short-term and long-term reproducibility for the GABA quantification were less than 10% when the frequency threshold was applied.

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